Anthrax is a deadly disease caused by the Gram-positive bacterium Bacillus anthracis. The organism infects humans and many other animals. The primary virulence factors are thought to be anthrax toxin and a glutamic acid capsule, both of which are encoded on large plasmids, although other important virulence factors may yet be discovered. Inhalation anthrax, the most severe form of the disease, results in a systemic infection in which the organism spreads to the lymph nodes and then into the blood where it is able to replicate at very high levels. The dissemination of anthrax spores into the air, which results in inhalation anthrax, is considered to be the most likely method by which this organism would be used as a biowarfare agent. The current vaccine for anthrax is thought to confer protection due to antibodies elicited by protective antigen. Future vaccines are likely to be based on this protein. We are taking a multifaceted approach to address the issues that CBER will face during the licensing of anthrax vaccines and in subsequent regulation of these products. We are initiating investigations in three general areas including 1) structure/function studies of virulence factors produced by B. anthracis, 2) genetics and gene regulation, and 3) evaluation of novel vaccine strategies. Because special monies for these projects were allocated relatively late in FY00, progress has just begun. Necessary strains, equipment and supplies are being acquired. Additional personnel are being recruited and hired.